An outbreak of a rare human pathogen — which was traced to the stagnant water in a newly constructed building a decade earlier — was solved by investigators at the National Institutes of Health (NIH) Clinical Center using a deep bank of isolates and cutting-edge molecular epidemiology.

In 2016, NIH clinicians detected a cluster of infections in six stem-cell transplant patients caused by Sphingomonas koreensis.¹ The bacteria are a rare cause of human infections, but looking back through the center’s large bank of isolates, they detected more infections, bringing the total to 12 patients since 2006. New construction in 2005 apparently allowed the bug to establish a reservoir in the disrupted water system.

“We were amazed that the organism had been dwelling in the building for so long and had changed so little,” says Tara Palmore, MD, hospital epidemiologist at the NIH Clinical Center.

Palmore and colleagues conducted whole-genome DNA sequencing on the clinical isolates, and cultured S. koreensis from the sinks and faucets in patient rooms and other areas.

“The investigation showed that two isolates of S. koreensis obtained from the six patients identified in the 2016 cluster were unrelated, but four isolates shared more than 99.92% genetic similarity and were resistant to multiple antibiotic agents,” they reported. “Retrospective analysis of banked clinical isolates of [S. koreensis] … revealed the intermittent recovery of a clonal strain over the past decade.”

Transmission Unknown

Following the cluster of cases in 2016, investigators looked for transmission sources. Overall, 22 of 56 cultures of water samples from faucets (39%) contained S. koreensis. The culture-positive rate rose to 53% if the samples were from faucets in the rooms of patients infected with the pathogen.

Investigators found one positive culture in a faucet directly linked to a patient, but the exact mode of transmission could not be determined for the cases, Palmore says.

“Some of the patients who acquired the organism were in the ICU and not using sinks,” she says. “It could have been water on the hands of healthcare workers. It also could have been water droplets aerosolized from sinks. We don’t know, but it could have been any of the ways that other waterborne organisms can be transmitted to patients.”

Although these were high-risk patients, three of the patients died. Moreover, the patient isolates and environmental samples were resistant to multiple antibiotics. That raises the question of how bacteria that are a rare source of human infection became so drug-resistant.

“We did not find any genes that conferred resistance to antibiotics, so this wasn’t acquired drug resistance,” Palmore says. “This wasn’t drug resistance of an organism that was hanging around hospitals and being exposed to antibiotics. It was built in to the coding of the DNA of the organism — it was just naturally drug-resistant.”

This phenomenon has been described before, perhaps most profoundly by investigators who found microbes in ancient, underground caves that were naturally resistant to antibiotics to which they could not possibly have been exposed.²

Journey to the Past

The NIH has a vast library of stored isolates, enabling investigators to look back in time and ultimately determine the origin of the reservoir.

“It’s actually amazing that our microbiology lab has [so many] isolates banked,” she says. “The lab has been deep-freezing isolates for decades. We can go back and do this kind of research and clinical investigation.”

Investigators also were surprised to discover that S. koreensis was even causing infections, and wanted to look back to see if prior cases had occurred.

“This is not the type of organism that normally gets a lot of attention in hospitals,” Palmore says.

“In fact, when I have presented this investigation at other hospitals, it really takes some convincing. I have to really go into the genomic data that we presented in the paper to get people to appreciate that this is something that they need to care about it.”

Infection preventionists may understandably be focused on time-honored water bugs such as Legionella and Pseudomonas, but the findings underscore that other waterborne pathogens need to be on the radar, she says.

“Another reason we went back and looked at frozen samples was because we knew that we had not always looked at Sphingomonas isolates to the species level,” she says.

“By genomic sequencing, we were able to identify whether there were any matches.”

Low Chlorine

Low chlorine levels in the hot water system were identified as the prime cause of the buildup of S. koreensis in the water system, Palmore and colleagues found.

“We found those low hot-water chlorine levels at the time we looked in 2016,” she says.

“We corrected the chlorine levels and monitored those closely. We’ve not had another case in going on two and a half years — since October 2016.”

Chlorine levels are now monitored at multiple sites in the hospital on an ongoing basis.

“We also culture water and follow those cultures,” she says. “Our research is ongoing into ways to reduce risk to patients.”

As IPs are well aware, in 2017 the Centers for Medicare & Medicaid Services released a memo mandating that “Medicare-certified healthcare facilities … have water management policies to reduce the risk of growth and spread of Legionella and other opportunistic pathogens in building water systems.”³

While certainly complying with the directive, Palmore warns that the CMS memo does not specifically require monitoring water chlorine levels — which the NIH regards as critical after the outbreak.

“It is important to pay particular attention to free chlorine concentrations,” she says.

“That is the major measure that suppresses the growth of many types of bacteria in water.”

Although many hospitals may not have such a deep store of isolates and genome sequencing technology, Palmore thinks other epidemiologists and IPs could have detected S. koreensis using common laboratory identification systems.

“The question is whether they would have recognized the importance of what they found,” she says.

“Whether they would have realized, if they found S. koreensis in a patient blood culture, that this is an organism they might need to be worried about.”

REFERENCES

1. Johnson RC, Deming C, Conlan S, et al. Investigation of a Cluster of Sphingomonas koreensis Infections. N Engl J Med 2018;379(26):2529-2539.
2. Spellberg B, Bartlett JG, Gilbert DN. The Future of Antibiotics and Resistance. N Engl J Med 2013;368:299-302.
3. CMS. Center for Clinical Standards and Quality/Survey & Certification Group. Requirement to Reduce Legionella Risk in Healthcare Facility Water Systems to Prevent Cases and Outbreaks of Legionnaires’ Disease (LD). Ref: S&C 17-30-ALL. June 02, 2017. Available at:
   http://go.cms.gov/2r3ue6B.